The Other Entrepreneurs: Giving Ailing Newborns a Fighting Chance From Vietnam


Hospitals of the world’s poorest countries.

Nga Tuyet Trang, the founder of Medical Technology Transfer and Services, orMTTS, is trying to make this happen.

After spending a year studying in Denmark in 2003, Nga returned home to Vietnam imagining a world where every infant, no matter where they were born, had an equal chance for a healthy life. Assembling an international team of specialists in biomedicine, mechanics, electronics and industrial design, she tasked them with adapting developed world medical equipment and practices to meet the needs of treating the most common problems affecting newborn babies at hospitals and clinics in developing countries.

Twelve years later, the outcome is MTTS’ range of low-cost, high-quality neonatal intensive care equipment. All made in Hanoi using readily available materials and parts, the machines are durable, easy to use and do not require expensive materials. Installed in more than 250 hospitals, MTTS equipment has so far been used to treat more than three-quarters of a million babies suffering from infant respiratory distress system, jaundice or hypothermia.

Hanoi, Vietnam

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Effect of double dose oseltamivir on clinical and virological outcomes in children and adults admitted to hospital with severe influenza: double blind randomised controlled trial.


Abstract

Objective To investigate the validity of recommendations in treatment guidelines to use higher than approved doses of oseltamivir in patients with severe influenza.

Design Double blind randomised trial.

Setting Thirteen hospitals in Indonesia, Singapore, Thailand, and Vietnam.

Participants Patients aged ≥1 year admitted to hospital with confirmed severe influenza.

Interventions Oral oseltamivir at double dose (150 mg twice a day/paediatric equivalent) versus standard dose (75 mg twice a day/paediatric equivalent).

Main outcome measure Viral status according to reverse transcriptase polymerase chain reaction (RT-PCR) for influenza RNA in nasal and throat swabs on day five.

Results Of 326 patients (including 246 (75.5%) children aged <15), 165 and 161 were randomised to double or standard dose oseltamivir, respectively. Of these, 260 (79.8%) were infected with influenza virus A (133 (40.8%) with A/H3N2, 72 (22.1%) with A/H1N1-pdm09, 38 (11.7%) with seasonal A/H1N1, 17 (5.2%) with A/H5N1) and 53 (16.2%) with influenza virus B. A further 3.9% (13) were false positive by rapid antigen test (negative by RT-PCR and no rise in convalescent haemagglutination inhibition titers). Similar proportions of patients were negative for RT-PCR on day five of treatment: 115/159 (72.3%, 95% confidence interval 64.9% to 78.7%) double dose recipients versus 105/154 (68.2%, 60.5% to 75.0%) standard dose recipients; difference 4.2% (−5.9 to 14.2); P=0.42. No differences were found in clearance of virus in subgroup analyses by virus type/subtype, age, and duration of illness before randomisation. Mortality was similar: 12/165 (7.3%, 4.2% to 12.3%) in double dose recipients versus 9/161 (5.6%, 3.0% to 10.3%) in standard dose recipients. No differences were found between double and standard dose arms in median days on supplemental oxygen (3 (interquartile range 2-5) v 3.5 (2-7)), in intensive care (4.5 (3-6) v 5 (2-11), and on mechanical ventilation (2.5 (1-16) v 8 (1-16)), respectively. No important differences in tolerability were found.

Conclusions There were no virological or clinical advantages with double dose oseltamivir compared with standard dose in patients with severe influenza admitted to hospital.

Discussion

In this large randomised controlled trial of antiviral treatment in patients with severe influenza we found that double dose oseltamivir was well tolerated but did not confer additional virological or clinical benefits over standard dose treatment in patients in South East Asia. There were no differences between the treatment arms in detection of viral RNA or infectious virus on day five, and there were also no differences in clinical failure rates, mortality in hospital, or rates of adverse events between the dose regimens on day five. We enrolled a heterogeneous population that included mostly children and also those infected with avian H5N1 or H1N1-pdm09 viruses. While subgroup analyses based on age cohorts, virus type and subtype, and time to treatment did not suggest additional virological efficacy of double dose oseltamivir in any subgroup, these results should be interpreted with caution as the study was not powered for these analyses.

Our patients presented relatively late after the onset of illness, a median of five days overall (seven days for H5N1). Despite administration of oseltamivir, about 30% of those enrolled remained positive for viral RNA (the primary endpoint) after five days of treatment. Timing of oseltamivir treatment is important as several studies have shown that early treatment confers greater virological and clinical benefits.4 5 6 32 33 34 In particular, later viral clearance has been noted with delayed treatment with oseltamivir compared with treatment within two to three days after onset of symptoms in observational reports from patients with H1N1-pdm09, especially those with severe illness.35 36 37 38 39 40 In the current trial, 73 (22.4%) patients presented within three days of illness, but even in this subpopulation, double dose oseltamivir was not associated with more rapid viral RNA clearance. Over a quarter of patients received neuraminidase inhibitors before enrolment, which could have influenced the effect size and contributed to the low proportion of patients shedding virus at day five in both treatment groups.

Although viral RNA detection in samples from the upper respiratory tract might not accurately reflect viral replication in the lower respiratory tract, especially in those with severe illness,39 prolonged viral RNA detection in upper respiratory tract samples has been shown to correlate with inpatient morbidity and prolonged hospital stay. In our study viral detection on day five was observed at about twofold the frequency in those meeting the criteria for clinical failure, although lack of clinical failure was not a surrogate for cessation of viral detection. Thus in our study the delays in starting treatment with oseltamivir also probably contributed to the substantial rates of admission to intensive care (18%), use of supplemental oxygen (30%), mechanical ventilation (12%), and mortality in hospital of 6.4%. Although our study was not placebo controlled for ethical reasons, other studies indicate that early oseltamivir treatment in people with severe influenza is associated with both clinical benefits and more rapid viral clearance from upper respiratory tract samples.

Possible reasons for findings

It is unclear why double dose oseltamivir does not seem to offer benefit over standard dose in patients with severe influenza. Blood trough concentrations of oseltamivir carboxylate from 75 mg or 150 mg twice daily in influenza exceed the IC50 (inhibitory concentration) of influenza viruses.42 43 Inhibition of viral neuraminidase by oseltamivir might be a saturable process, and maximal inhibition might be achieved with a standard dose; exceeding these concentrations might not produce an additional clinical or virological effect. In this regard, a randomised oseltamivir controlled study of intravenous peramivir (BioCryst Pharmaceuticals, Durham, NC), which reaches over 20-fold higher peak blood concentrations of active metabolite than oseltamivir carboxylate, found similar viral reductions in patients with influenza A virus admitted to hospital.44 Further studies of peramivir and other intravenous neuraminidase inhibitors currently in progress should provide additional evidence regarding this hypothesis.

Infection with avian H5N1 virus, higher baseline viral load, and severity of disease were independently associated with longer viral RNA detection. The association between avian H5N1, severe illness, and prolonged shedding has been well described.14 The clearance kinetics of influenza viruses, both without antiviral treatment and with oseltamivir treatment,32 41 could explain longer viral RNA detection with higher baseline viral loads. It is unclear whether the independent association with disease severity might be related to impaired mechanisms of viral clearance or higher intrinsic rates of viral replication or both in these patients. Severe chronic comorbidities are seen commonly in industrialised countries and are related to prolonged viral shedding but most of our patients lacked these comorbidities.40 41

The heterogeneous population characteristics, geographical differences in recruitment (most patients were from Vietnam but there were no significant differences between Vietnam and other sites), and the variety of infecting viruses in our trial reflect the clinical circumstances in South East Asia during our study but might be viewed as a limitation. Most of these patients were children and had low or normal BMI, and for all patients only about a fifth reported a chronic underlying medical condition. Thus, our findings are applicable primarily to the region where the study was conducted and other settings with similar characteristics of influenza epidemiology. We did not have many adults in our study and results were inconclusive but indicate no difference in efficacy between the two oseltamivir regimens. We would caution the extension of our results to, for example, morbidly obese adults with severe influenza and those who could have underlying chronic illnesses. We conducted several statistical comparisons and inevitably subgroup analyses involved small numbers; thus power was limited and some significant results could have resulted by chance. Additionally, as all patients were randomised to an active treatment, our study was not designed to evaluate the efficacy of oseltamivir in severe influenza nor in H5N1 infections. This large randomised trial did, however, examine an important clinical and public health question and showed a lack of a clinical or virological benefit of double dose compared with standard dose oseltamivir in patients admitted to hospital with severe influenza. Our results and other observational reports from avian H5N110 and H1N1-pdm0911 36 infections do not support routine use of double dose oseltamivir to treat severe influenza. These findings have implications for both clinical management and pandemic preparedness including during the current H7N9 epidemic.16 17 18

What is already known on this topic

  • Clinical trials in patients with uncomplicated influenza have shown that treatment with oseltamivir has clinical and virological benefit when administered within 48 hours of onset of symptoms
  • Observational studies in severe influenza have shown that oseltamivir treatment, if given early, is associated with reduced mortality and shorter length of hospital stay. Reduced mortality has also been reported for patients with H5N1 influenza treated with oseltamivir
  • Several authorities have suggested the use of double dose oseltamivir for severe influenza, although there is no clinical evidence to support this
  • In the largest randomised trial on the treatment of severe influenza, no clinical or virological benefit of double dose oseltamivir over standard dose was found
  • These findings have implications for both clinical management of severe influenza and for pandemic preparedness of emerging influenza viruses including the current H7N9 epidemic

What this study adds

 

 

Source: BMJ

 

 

Effect of double dose oseltamivir on clinical and virological outcomes in children and adults admitted to hospital with severe influenza: double blind randomised controlled trial.


Abstract

Objective To investigate the validity of recommendations in treatment guidelines to use higher than approved doses of oseltamivir in patients with severe influenza.

Design Double blind randomised trial.

Setting Thirteen hospitals in Indonesia, Singapore, Thailand, and Vietnam.

Participants Patients aged ≥1 year admitted to hospital with confirmed severe influenza.

Interventions Oral oseltamivir at double dose (150 mg twice a day/paediatric equivalent) versus standard dose (75 mg twice a day/paediatric equivalent).

Main outcome measure Viral status according to reverse transcriptase polymerase chain reaction (RT-PCR) for influenza RNA in nasal and throat swabs on day five.

Results Of 326 patients (including 246 (75.5%) children aged <15), 165 and 161 were randomised to double or standard dose oseltamivir, respectively. Of these, 260 (79.8%) were infected with influenza virus A (133 (40.8%) with A/H3N2, 72 (22.1%) with A/H1N1-pdm09, 38 (11.7%) with seasonal A/H1N1, 17 (5.2%) with A/H5N1) and 53 (16.2%) with influenza virus B. A further 3.9% (13) were false positive by rapid antigen test (negative by RT-PCR and no rise in convalescent haemagglutination inhibition titers). Similar proportions of patients were negative for RT-PCR on day five of treatment: 115/159 (72.3%, 95% confidence interval 64.9% to 78.7%) double dose recipients versus 105/154 (68.2%, 60.5% to 75.0%) standard dose recipients; difference 4.2% (−5.9 to 14.2); P=0.42. No differences were found in clearance of virus in subgroup analyses by virus type/subtype, age, and duration of illness before randomisation. Mortality was similar: 12/165 (7.3%, 4.2% to 12.3%) in double dose recipients versus 9/161 (5.6%, 3.0% to 10.3%) in standard dose recipients. No differences were found between double and standard dose arms in median days on supplemental oxygen (3 (interquartile range 2-5) v 3.5 (2-7)), in intensive care (4.5 (3-6) v 5 (2-11), and on mechanical ventilation (2.5 (1-16) v 8 (1-16)), respectively. No important differences in tolerability were found.

Conclusions There were no virological or clinical advantages with double dose oseltamivir compared with standard dose in patients with severe influenza admitted to hospital.

Discussion

In this large randomised controlled trial of antiviral treatment in patients with severe influenza we found that double dose oseltamivir was well tolerated but did not confer additional virological or clinical benefits over standard dose treatment in patients in South East Asia. There were no differences between the treatment arms in detection of viral RNA or infectious virus on day five, and there were also no differences in clinical failure rates, mortality in hospital, or rates of adverse events between the dose regimens on day five. We enrolled a heterogeneous population that included mostly children and also those infected with avian H5N1 or H1N1-pdm09 viruses. While subgroup analyses based on age cohorts, virus type and subtype, and time to treatment did not suggest additional virological efficacy of double dose oseltamivir in any subgroup, these results should be interpreted with caution as the study was not powered for these analyses.

Our patients presented relatively late after the onset of illness, a median of five days overall (seven days for H5N1). Despite administration of oseltamivir, about 30% of those enrolled remained positive for viral RNA (the primary endpoint) after five days of treatment. Timing of oseltamivir treatment is important as several studies have shown that early treatment confers greater virological and clinical benefits.4 5 6 32 33 34 In particular, later viral clearance has been noted with delayed treatment with oseltamivir compared with treatment within two to three days after onset of symptoms in observational reports from patients with H1N1-pdm09, especially those with severe illness.35 36 37 38 39 40 In the current trial, 73 (22.4%) patients presented within three days of illness, but even in this subpopulation, double dose oseltamivir was not associated with more rapid viral RNA clearance. Over a quarter of patients received neuraminidase inhibitors before enrolment, which could have influenced the effect size and contributed to the low proportion of patients shedding virus at day five in both treatment groups.

Although viral RNA detection in samples from the upper respiratory tract might not accurately reflect viral replication in the lower respiratory tract, especially in those with severe illness,39 prolonged viral RNA detection in upper respiratory tract samples has been shown to correlate with inpatient morbidity and prolonged hospital stay. In our study viral detection on day five was observed at about twofold the frequency in those meeting the criteria for clinical failure, although lack of clinical failure was not a surrogate for cessation of viral detection. Thus in our study the delays in starting treatment with oseltamivir also probably contributed to the substantial rates of admission to intensive care (18%), use of supplemental oxygen (30%), mechanical ventilation (12%), and mortality in hospital of 6.4%. Although our study was not placebo controlled for ethical reasons, other studies indicate that early oseltamivir treatment in people with severe influenza is associated with both clinical benefits and more rapid viral clearance from upper respiratory tract samples.4 8 14 36 37 38 39 40 41

Possible reasons for findings

It is unclear why double dose oseltamivir does not seem to offer benefit over standard dose in patients with severe influenza. Blood trough concentrations of oseltamivir carboxylate from 75 mg or 150 mg twice daily in influenza exceed the IC50 (inhibitory concentration) of influenza viruses.42 43 Inhibition of viral neuraminidase by oseltamivir might be a saturable process, and maximal inhibition might be achieved with a standard dose; exceeding these concentrations might not produce an additional clinical or virological effect. In this regard, a randomised oseltamivir controlled study of intravenous peramivir (BioCryst Pharmaceuticals, Durham, NC), which reaches over 20-fold higher peak blood concentrations of active metabolite than oseltamivir carboxylate, found similar viral reductions in patients with influenza A virus admitted to hospital.44 Further studies of peramivir and other intravenous neuraminidase inhibitors currently in progress should provide additional evidence regarding this hypothesis.

Infection with avian H5N1 virus, higher baseline viral load, and severity of disease were independently associated with longer viral RNA detection. The association between avian H5N1, severe illness, and prolonged shedding has been well described.14 The clearance kinetics of influenza viruses, both without antiviral treatment and with oseltamivir treatment,32 41 could explain longer viral RNA detection with higher baseline viral loads. It is unclear whether the independent association with disease severity might be related to impaired mechanisms of viral clearance or higher intrinsic rates of viral replication or both in these patients. Severe chronic comorbidities are seen commonly in industrialised countries and are related to prolonged viral shedding but most of our patients lacked these comorbidities.40 41

The heterogeneous population characteristics, geographical differences in recruitment (most patients were from Vietnam but there were no significant differences between Vietnam and other sites), and the variety of infecting viruses in our trial reflect the clinical circumstances in South East Asia during our study but might be viewed as a limitation. Most of these patients were children and had low or normal BMI, and for all patients only about a fifth reported a chronic underlying medical condition. Thus, our findings are applicable primarily to the region where the study was conducted and other settings with similar characteristics of influenza epidemiology. We did not have many adults in our study and results were inconclusive but indicate no difference in efficacy between the two oseltamivir regimens. We would caution the extension of our results to, for example, morbidly obese adults with severe influenza and those who could have underlying chronic illnesses. We conducted several statistical comparisons and inevitably subgroup analyses involved small numbers; thus power was limited and some significant results could have resulted by chance. Additionally, as all patients were randomised to an active treatment, our study was not designed to evaluate the efficacy of oseltamivir in severe influenza nor in H5N1 infections. This large randomised trial did, however, examine an important clinical and public health question and showed a lack of a clinical or virological benefit of double dose compared with standard dose oseltamivir in patients admitted to hospital with severe influenza. Our results and other observational reports from avian H5N110 and H1N1-pdm0911 36 infections do not support routine use of double dose oseltamivir to treat severe influenza. These findings have implications for both clinical management and pandemic preparedness including during the current H7N9 epidemic.16 17 18

What is already known on this topic

  • Clinical trials in patients with uncomplicated influenza have shown that treatment with oseltamivir has clinical and virological benefit when administered within 48 hours of onset of symptoms
  • Observational studies in severe influenza have shown that oseltamivir treatment, if given early, is associated with reduced mortality and shorter length of hospital stay. Reduced mortality has also been reported for patients with H5N1 influenza treated with oseltamivir
  • Several authorities have suggested the use of double dose oseltamivir for severe influenza, although there is no clinical evidence to support this
  • In the largest randomised trial on the treatment of severe influenza, no clinical or virological benefit of double dose oseltamivir over standard dose was found
  • These findings have implications for both clinical management of severe influenza and for pandemic preparedness of emerging influenza viruses including the current H7N9 epidemic

What this study adds

 

Source: BMJ

 

Why China isn’t taking American trash anymore.


china-garbage-landfill-bw-flickr

Quick, what’s the biggest U.S. export to China?

Soybeans?

Officially, yes, it’s the biggest single product. But combined, the U.S. exports more scrap and waste to China than any other single product — $11.31 billion in 2011. Growth of waste exports has been quick and steep. In 1997, only $182 million worth of waste went to China. But expect that growth to come to a screeching halt.

That’s because China no longer wants all that U.S. waste, as Gwynn Guilford reports at Quartz:

[H]ints are emerging that American cities and the companies that sell trash are in for a rude awakening. A recent sign of this comes from Oregon, where truckloads of plastic are piling up at recycling depots because Chinese buyers cancelled their orders, as Oregon Public Broadcasting reports.

And it’s not just plastic from Oregon. American waste recycling companies are starting to panic. “What I’m hearing from folks in the industry, it’s that just that nothing is going,” the industry insider says. “[China’s] not taking anything anymore. It’s a greenwall.”

More specifically, China’s implemented a policy called Operation Green Fence. The policy cracks down on the amount of contaminants that can be included in a bale of waste, including unwashed plastics and other banned materials, leading to “severe recycling market confusion worldwide.”

It’s hitting the recycling industry especially hard. Global shipments of recovered paper to China are down 18.4 percent. And prices for recovered materials are dropping.

It’s easy to forget that recycling is an industry. As one industry insider told Quartz, “The public doesn’t realize this, but recycling is made possible by technology and markets—they think it’s just a matter of technology. And we don’t have strong enough markets in the US.”

So happens next? One industry source says the initiative will end in November. But for now, other countries could take what the U.S. currently ships to China. Vietnam is a potential source. In the short term it could mean a lot of plastics just end up in the landfill. But in the long term it could lead to more innovation in the industry.

For now, it’s just a mess.

Source: Smart planet

‘Penis-head’ fish discovered in Vietnam.


A preserved specimen of Phallostethus cuulong, a new species of fish with a penis on its head that has been identified in the Mekong delta in Vietnam. Researchers said Wednesday that Phallostethus cuulong is the newest member of the Phallostethidae family—small fish found in Southeast Asian waters that are distinguished primarily by the positioning of the male sexual organ. A new species of fish with a penis on its head has been identified in the Mekong Delta in Vietnam, researchers said on Wednesday. Ads by Google Pregnancy – Everything you wanted to know what to do during pregnancy. – http://www.StartHealthyStayHealthy.in Phallostethus cuulong is the newest member of the Phallostethidae family—small fish found in Southeast Asian waters that are distinguished primarily by the positioning of the male sexual organ. Male phallostethids have a copulatory organ, termed the priapium, under the throat for holding or clasping onto females and fertilising their eggs internally, according to conservationists. “We have scientifically identified a new penis-head fish in Vietnam,” researcher Tran Dac Dinh from Can Tho University told AFP. The fish was known to Vietnamese people in the Mekong Delta but had not been described scientifically before a team identified the species last year, he said. 

Read more at: http://phys.org/news/2012-08-penis-head-fish-vietnam.html#jCp

Source: Physics.org